Identification of heterozygous variants in the LPL and LMF1 genes in patients with severe hypertriglyceridemia.

Abstract

Hypertriglyceridemia (HTG) is a disorder of lipid metabolism characterized by an increase in the level of triglycerides (TG) in blood plasma of more than 1,7 mmol/l. The level of TG ≥10 mmol/l, according to some literature data, or ≥ 11.2 mmol/l, according to others, is considered a severe form of HTG. A number of factors are responsible for the development of this pathology: pathogenic or likely pathogenic variants in the gene or genes associated with HTG, the presence of metabolic diseases, environmental factors, and lifestyle. The most dangerous phenotypic manifestation of elevated TG levels in blood plasma is the development of acute pancreatitis, for which patients often seek medical help for the first time. In this study, we describe two clinical cases of severe HTG that we observed, in which the diagnostic search consisted of molecular genetics and instrumental methods. As a result of the study of the biological material of patients by sequencing, the following were identified: in the first case, a heterozygous, probably pathogenic variant in the LPL gene and a probably benign variant in the LMF1 gene; in the second, a heterozygous variant of unclear clinical significance in the LMF1 gene. The article discusses the possible causal role of these genetic variants and the complexity of the clinical interpretation of heterozygous causes of HTG.